Regulation of SLD5 gene expression by miR-370 during acute growth of cancer cells

Abstract

SLD5 is a member of the GINS complex, essential for DNA replication in eukaryotes. It has been reported that SLD5 is involved in early embryogenesis in the mouse, and cell cycle progression and genome integrity in Drosophila. SLD5 may be involved in malignant tumor progression, but its relevance in human cancer has not been determined. Here, we found strong SLD5 expression in both human bladder cancer tissues from patients and cell lines. Knockdown of SLD5 using small interfering RNA resulted in reduction of cell growth both in vitro and an in vivo xenograft model. Moreover, we found that high levels of SLD5 in bladder cancer cells result from downregulation of microRNA (miR)-370 that otherwise suppresses its expression. High level expression of DNA-methyltransferase (DNMT) 1 and IL-6 were also observed in bladder cancer cells. Knockdown of IL-6 led to downregulation of DNMT1 and SLD5 expression, suggesting that IL-6-induced overexpression of DNMT1 suppresses miR-370, resulting in high SLD5 expression. Our findings could contribute to understanding tumorigenic processes and progression of human bladder cancer, whereby inhibition of SLD5 could represent a novel strategy to prevent tumor growth.

Influenza virus matrix protein M1 interacts with SLD5 to block host cell cycle

“…Previous studies indicate that targeted disruption of SLD5 in mice causes defective cell proliferation in the inner cell mass, resulting in embryonic lethality (Mohri et al, 2013). Knockdown of SLD5 reduces the expression of cell proliferation marker Ki-67 (Yamane et al, 2016), and attenuation of SLD5 delays DNA repair responses and cell cycle restoration in normal cells (Gong, Kidoya, Mohri, Han, & Takakura, 2014). In this study, we show that M1 interacts with SLD5 resulting in arrested host cell cycle progression.…”

“…Influenza virus infection causes severe damage to the bronchial and alveolar epithelial cells (Kumar et al, 2013a). Previous studies have shown that disruption of SLD5 causes defective cell cycle restoration and cell proliferation (Mohri et al, 2013;Yamane et al, 2016).…”

“…SLD5 partially rescues influenza-induced G0/G1 arrest. Previous studies have shown that disruption of SLD5 causes defective cell cycle restoration and cell proliferation(Mohri et al, 2013;Yamane et al, 2016). A549 cells stably expressing SLD5 or control cells were serum-starved for 48 hr, and then mock infected or infected with PR8 virus at MOIs of 0.1 and 1.…”

Microdevices for Non-Invasive Detection of Bladder Cancer

“…Proteins involved in apoptosis, such as Bcl-2 and caspase-3, also presented potential as survival predictors. Other studies also reported aberrant protein expression in bladder cancer tissue, such as the overexpression of SLD5 [45]. The expression levels of pAkt, PTEN, Drg-1, Cx-26, and L-plastin were often correlated with tumor grade and stage, as well as other clinicopathological features of bladder cancer.…”

“…p21, p53, pRB, and p27 [44] Bcl-2 and caspase-3 [45] pAkt, PTEN, Drg-1, Cx-26, and L-plastin [46] CXCL16 and CXCR6 [47] CXCR4 [48] CxBladder Detect Test for the presence of mRNA associated with cancer-linked genes IGF, HOXA, MDK, CDC, and IL8R [49] UroVysion Detect aneuploidy and loss of loci from patient's urine sample via fluorescence in situ hybridization (FISH).…”